16-27618340-G-C

Position:

• chr16-27618340-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_015202.5(KATNIP):​c.64-85G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.859 in 1,059,112 control chromosomes in the GnomAD database, including 391,947 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.85 (54896 hom., cov: 31)
  • Exomes 𝑓: 0.86 (337051 hom.)
• Consequence: KATNIP NM_015202.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.159

Genes affected

KATNIP (HGNC:29068): (katanin interacting protein) This gene encodes a novel, evolutionarily conserved, ciliary protein. In human hTERT-RPE1 cells, the protein is found at the base of cilia, decorating the ciliary axoneme, and enriched at the ciliary tip. The protein binds to microtubules in vitro and regulates their stability when it is overexpressed. A null mutation in this gene has been associated with Joubert syndrome, a recessive disorder that is characterized by a distinctive mid-hindbrain and cerebellar malformation and is also often associated with wider ciliopathy symptoms. Consistently, in a serum-starvation ciliogenesis assay, human fibroblast cells derived from patients with the mutation display a reduced number of ciliated cells with abnormally long cilia. [provided by RefSeq, Feb 2016]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 16-27618340-G-C is Benign according to our data. Variant chr16-27618340-G-C is described in ClinVar as [Benign]. Clinvar id is 1250543.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.974 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KATNIP	NM_015202.5	c.64-85G>C		intron_variant		ENST00000261588.10	NP_056017.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KATNIP	ENST00000261588.10	c.64-85G>C		intron_variant		1	NM_015202.5	ENSP00000261588.4
KATNIP	ENST00000568258.5	c.49-85G>C		intron_variant		3		ENSP00000454884.1
KATNIP	ENST00000565672.5	n.34-10321G>C		intron_variant		3		ENSP00000455380.1

Frequencies

GnomAD3 genomes AF: 0.849 AC: 129094 AN: 152072 Hom.: 54851 Cov.: 31

Gnomad AFR AF: 0.826

Gnomad AMI AF: 0.886

Gnomad AMR AF: 0.832

Gnomad ASJ AF: 0.812

Gnomad EAS AF: 0.997

Gnomad SAS AF: 0.941

Gnomad FIN AF: 0.877

Gnomad MID AF: 0.804

Gnomad NFE AF: 0.846

Gnomad OTH AF: 0.844

GnomAD4 exome AF: 0.861 AC: 780686 AN: 906922 Hom.: 337051 AF XY: 0.864 AC XY: 407350 AN XY: 471278

Gnomad4 AFR exome AF: 0.829

Gnomad4 AMR exome AF: 0.832

Gnomad4 ASJ exome AF: 0.800

Gnomad4 EAS exome AF: 0.999

Gnomad4 SAS exome AF: 0.937

Gnomad4 FIN exome AF: 0.879

Gnomad4 NFE exome AF: 0.848

Gnomad4 OTH exome AF: 0.854

GnomAD4 genome AF: 0.849 AC: 129193 AN: 152190 Hom.: 54896 Cov.: 31 AF XY: 0.849 AC XY: 63188 AN XY: 74394

Gnomad4 AFR AF: 0.826

Gnomad4 AMR AF: 0.832

Gnomad4 ASJ AF: 0.812

Gnomad4 EAS AF: 0.997

Gnomad4 SAS AF: 0.941

Gnomad4 FIN AF: 0.877

Gnomad4 NFE AF: 0.846

Gnomad4 OTH AF: 0.845

Alfa AF: 0.846 Hom.: 6420

Bravo AF: 0.844

Asia WGS AF: 0.968 AC: 3365 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	6.3
DANN	Benign	0.65

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs4787980; hg19: chr16-27629661;